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D S Postma

Publications and source records attributed to D S Postma.

At least 181 records · Page 10Linked to original sources
PubMed1998

Submucosa 1.0 x 0.1 mm in size is sufficient to count inflammatory cell numbers in human airway biopsy specimens.

Counting of inflammatory cells in human airway biopsy specimens is difficult because immunopositive cells are present in varying density in lung tissue. The goal of our study was to assess the minimal amount of tissue that is necessary for the counting of constant cell numbers. In bronchial biopsy specimens from 5 healthy controls and 5 patients with asthma, we evaluated 20 successive areas of submucosa 0.1 x 0.1 mm in size. We recorded positive and negative changes of more than 10% in the counted numbers of CD4-, CD8-, and EG2-positive cells. We demonstrated that tissue 1.0 x 0.1 mm in size, along 1-mm basement membrane, is sufficient to obtain constant cell numbers.

Asthma↗
PubMed1998

Macrophages in lung tissue from patients with pulmonary emphysema express both inducible and endothelial nitric oxide synthase.

To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-related emphysema, we performed immunohistochemical studies in lung tissue from control subjects and patients with mild and severe emphysema. We studied the presence of inducible and endothelial NO synthases (iNOS and eNOS, respectively) and determined nicotinamide diphosphate (NADPH) diaphorase activity. Patients with severe emphysema showed lower percentages of iNOS- and eNOS-positive alveolar macrophages in situ than did patients with mild emphysema. In patients with both iNOS and eNOS immunoreactivity in macrophages, the majority of the macrophages expressed either iNOS or eNOS, whereas only a minority of the macrophages showed iNOS and eNOS immunoreactivity simultaneously. Immunoreactivity for eNOS in endothelial and/or bronchiolar epithelial cells and NADPH diaphorase activity in macrophages and in endothelial, epithelial, and smooth muscle cells were similar in the three studied groups. The expression of eNOS in macrophages suggests that eNOS plays an additional role, besides iNOS, in the NO housekeeping in inflammatory processes in pulmonary tissue. We suggest that NO might have a protective role in maintenance of structural integrity of pulmonary tissue after smoke-induced damage.

Adolescent↗
PubMed1997

Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.

BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.

Administration, Inhalation↗
PubMed1997

The impact of day care on ventilation tube insertion.

OBJECTIVE: To study the effect of day care and tube type, as well as other risk factors related to ventilation tube insertion and reinsertion. DESIGN: A case series of 456 consecutive cases with 162 controls from a well-baby examination group evaluated for age, sex, smoking history and day care attendance. SETTING: Private practice in a mid-sized, southeastern university town. PATIENTS AND CONTROLS: This was a referred sample of patients who were entered consecutively in a private-practice setting. All children were age five or less at entry into the study. INTERVENTIONS: Children underwent ventilation tube insertion with or without adenoidectomy, using standing indications. MAIN OUTCOME MEASURES: The primary outcome measures were whether or not a child had the need for a second set of tubes, and also determining the status of the child's ears for at least 1 year after tubes had extruded. RESULTS: Day care and younger age were both identified as risk factors associated with initial ventilation tube insertion. Only 11% (seven out of 63) of home care children, as compared with 31% (108 out of 346) day care children, had the insertion of ventilation tubes (P = 0.000). Day care children who had tubes inserted and adenoidectomy (with or without tonsillectomy) had a significantly lower rate of reintubation than children who had tube insertion alone (P = 0.00). Day care and young age are significant risk factors for any child, both with a first set of tubes and for ventilation tube reinsertion. Children in day care had a reintubation rate of 36% as compared to 11% for those in home care. Parents should be aware that day care can represent a two-fold hazard both in the observed connection between day care and tube insertion and the demonstrated increased probability of reinsertion. Any studies looking at ventilation tube outcomes need to make certain to monitor for day care attendance.

Adenoidectomy↗
PubMed1997

Genetic susceptibility to asthma in a changing environment.

There is a major interest in investigating the genetic components of allergy and asthma. Four different areas are involved in the study of complex genetic diseases: family studies, assessment of phenotype, segregation analysis and gene mapping. Initial assessment of phenotype must be practical, reproducible and relatively independent of compounding variables. Phenotypes important in allergy and asthma include atopic parameters such as total serum IgE, bronchial hyper-responsiveness and the presence/ absence of clinical asthma. Numerous family and twin studies have suggested the presence of a heritable component for allergy, bronchial hyper-responsiveness and asthma. The number of genes involved in these complex genetic disorders and their mode of inheritance have not been fully determined. Our group has been involved in a collaborative US-Dutch study in which 92 families with over 500 individuals have been phenotyped and DNA has been obtained for genotyping. Initial results of the classification of family members show that approximately 26% of the offspring of families ascertained through a parent with asthma have an asthmatic phenotype. A large number of these offspring with clinical evidence of asthma do not have a prior physician diagnosis of asthma, suggesting that there is a spectrum which ranges from preclinical to symptomatic asthma. The familial aggregation of asthma and other obstructive airway diseases in these families is consistent with a significant genetic component. Initial linkage studies have been performed on two characteristics of the allergic and asthmatic phenotype. Total serum IgE was analysed because this measure correlates with the clinical expression of allergy, bronchial hyper-responsiveness and asthma. Segregation analysis of total serum IgE provided evidence for a recessive mode of inheritance. Sib pair analyses and maximum likelihood scores suggest that a gene regulating IgE production maps to chromosome 5q. Bronchial hyper-responsiveness and total serum IgE are related to asthma in population-based studies. Sib pair analyses for bronchial responsiveness showed significant linkage to markers on chromosome 5q.

Asthma↗
PubMed1997

Respiratory muscle activity and pulmonary function during acutely induced airways obstruction.

BACKGROUND: Patients with airway obstruction may spontaneously breathe with a positive expiratory pressure by pursing their lips during expiration, especially in case of dyspnea. Dyspnea seems to be related to increased activity of the respiratory muscles. A potential explanation for the use of pursed lips breathing (PLB) is that this type of breathing leads to a reduction of respiratory muscle activity. The purpose of this study was to assess the effect of breathing with a positive expiratory pressure of 5 cm H2O, simulating pursed lips breathing (SPLB), on respiratory muscle activity and pulmonary function during induced airway obstruction. METHODS: In twelve asthmatic patients, tonic and phasic electromyographic (EMG) activity of the following muscles was obtained: scalene muscle, parasternal muscle, and abdominal muscles. Pulmonary function and EMG measurements were performed before and after propranolol induced airway obstruction. RESULTS: Simulated pursed lips breathing resulted in a significant increase of functional residual capacity and tidal volume both at baseline and during airway obstruction. Phasic respiratory muscle activity during PEP breathing increased especially at baseline. We conclude that beneficial effects of breathing with a positive expiratory pressure of 5 cm H2O, which is similar to pursed lips breathing, cannot be explained by changes in respiratory muscle activity or pulmonary function.

Acute Disease↗
PubMed1997

Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease: association with smoking, IgE and lung function.

In contrast to the numerous studies which show that lymphocytes play an important role in the pathogenesis of asthma, few studies have investigated the role of lymphocytes in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate lymphocyte subsets in peripheral venous blood of smoking and non-smoking COPD patients and healthy controls. The interaction of smoking and IgE has also been assessed, and it was investigated whether a lower level of FEV1 was associated with changes in lymphocyte subsets. In the present study, peripheral venous blood lymphocyte subsets were investigated in 42 smoking and non-smoking, non-atopic subjects with a clear diagnosis of COPD (43-74 years) who all used bronchodilator therapy only, and in 24 normal, healthy control subjects (40-72 years). No significant differences in lymphocyte subsets were found when either total groups or smoking subjects of both groups were compared. However, the percentage of CD8+ lymphocytes (suppressor/ cytotoxic T-cells) was significantly higher in the non-smoking COPD subjects compared with the non-smoking, healthy control subjects (P < 0.05). In addition, within the group of non-smoking COPD subjects, a higher CD4:CD8 ratio was associated with a higher FEV1 as a percentage of predicted (% pred.) (r = 0.55, P = 0.01) and a lower total serum IgE (r = -0.45, P = 0.04). Within the group of smoking COPD subjects, a higher FEV1 % pred. was associated with a higher percentage of CD19+ lymphocytes (B-cells) (r = 0.65, P < 0.01). The present study provides further evidence that the changes in the balance of T-cell subsets and IgE synthesis possibly plays a role in the pathogenesis of COPD.

Adult↗
PubMed1997

Discriminative aspects of two generic and two asthma-specific instruments: relation with symptoms, bronchodilator use and lung function in patients with mild asthma.

The objective of this study was to compare the two most frequently used asthma-specific quality of life (QOL) questionnaires and two generic QOL questionnaries with clinical data in order to establish their ability to discriminate in asthma severity, also referred to as cross-sectional construct validity. We conducted a multicentre, randomized, placebo-controlled study investigating the long-term effects of the long-acting beta 2-agonist formoterol in asthma patients using inhaled corticosteroids and short-acting beta 2-agonists. Before randomization, the peak expiratory flow (PEF) and use of beta 2-agonists for relief of symptoms were recorded twice daily for 1 month. At the end of the run-in period, the forced expiratory volume in 1 s (FEV1), airway hyper-responsiveness (PC20 methacholine) and QOL were measured, using two asthma-specific questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Living with Asthma Quality of Life Questionnaire (LWAQ), as well as two generic questionnaires, the Short Form 36 (SF-36) and the Psychological General Well Being (PGWB) index. The quality of life of the patients (n = 110) was only mildly impaired. The mean symptom score was 3.6 on a scale of 0-21 and the mean FEV1 was 65% of that predicted. The correlations between the QOL parameters and objective measures of asthma severity, such as the FEV1, PEF and PC20, were low (0.01-0.37). The correlations between the QOL parameters and subjective measures of asthma severity, such as symptom scores (range 0.26-0.65) and beta 2-agonist use for the relief of symptoms (0.09-0.39), were higher. The correlations of the activity and symptoms domains of the AQLQ with diary-obtained symptom scores were r = 0.50 (p < 0.0001) and r = 0.65 (p < 0.0001), respectively. The correlation between the physical construct of the LWAQ and symptom scores was r = 0.42 (p < 0.001) and that between the physical sumscore of the SF-36 and symptom scores was r = 0.50 (p < 0.001). The correlation between the PGWB and symptom scores was r = 0.41 (p < 0.001). The relation between the FEV1, PEF and PC20 and QOL was very low. The QOL measurements related well to the symptom scores. The AQLQ had a better cross-sectional construct validity than the LWAQ. The cross-sectional construct validity of the SF-36 was surprisingly high for this group of patients and the SF-36 performed better than the PGWB and LWAQ.

Adrenergic beta-Agonists↗
PubMed1997

Picumeterol: dissociation of improvement in lung function and reduction of airways hyperresponsiveness in asthmatics.

AIMS: The new potent and selective beta 2-adrenoceptor agonist, GR 114297A (picumeterol) is the R-enantiomer of the racemic form, GR 63411B. Picumeterol has been shown to produce long-lasting relaxation of airways smooth muscle both in vitro and in vivo. We assessed the intrinsic activity of picumeterol by increasing intracellular levels of c-AMP and compared this with isoprenaline and salbutamol. METHODS: In human atopic asthmatics, we have investigated the duration of action and efficacy of picumeterol and GR 63411B with regard to improvement in resting lung function (i.e. FEV1) and airways responsiveness (i.e. PC20) to methacholine (MCh). The study design consists of two clinical parts each for one drug. Different asthmatics participated in the two studies, seven in the first part and eight in the second part. In human bronchial smooth muscle cells in vitro, we have investigated the intrinsic activity of picumeterol in increasing intracellular levels of cyclic AMP and compared it with isoprenaline and salbutamol. RESULTS: In vivo, both drugs caused bronchodilatation with similar potency, but, their effects were short-lasting. Despite their bronchodilator activity, neither drug improved PC20, when compared with placebo. In vitro, picumeterol was found have intrinsic activity lower than the other beta 2-adrenoceptor agonists tested. CONCLUSIONS: In the clinical studies, the bronchodilator potencies of picumeterol and GR 63411B were similar. However, both drugs were short-acting, which is at odds with their activity in vitro. Our data suggest that these compounds display dissociation between bronchodilator activity and protection against MCh-induced bronchoconstriction. These findings may be explained by low intrinsic activity and need further conformation.

Adrenergic beta-2 Receptor Agonists↗
PubMed1997

Effects of the long acting beta agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. The Netherlands and Canadian Formoterol Study Investigators.

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.

Adrenergic beta-Agonists↗
PubMed1997

Fluticasone propionate, salmeterol xinafoate, and their combination in the treatment of nocturnal asthma.

Inhaled corticosteroids have been shown to effectively reduce large circadian fluctuations in peak expiratory flow (PEF). Salmeterol xinafoate (SLM), a new long-acting beta2-agonist being used in the treatment of nocturnal airway obstruction, has proved to be very effective in this respect as well. However, it is yet unknown whether using SLM alone or in combination with fluticasone propionate (FP) constitutes the best treatment. We studied, in a randomized, double-blind, parallel manner, 46 asthmatics with increased circadian variation in PEF (> or = 15%) for 6 wk to compare FP 250 microg, SLM 50 microg, and a combination of them, all given twice a day. These three treatment protocols were equally effective in improving the generally used clinical outcome parameters, i.e., the circadian variation in PEF and FEV1 and bronchial hyperresponsiveness (BHR) to methacholine (MCh) during the day and at night. FEV1 increased more at 4:00 A.M. than at 4:00 P.M. (FEV1 at both time points > 90% predicted). BHR to MCh improved with at least 1.5 doubling concentrations, thereby reducing the significant nocturnal decline in the SLM and FP group, but not in combination. The improvement in BHR to adenosine 5'monophosphate was greater (p = 0.05) when FP was combined with SLM but not when FP or SLM were used alone. Our data support the clinical view that FP, with its anti-inflammatory capacity, has greater beneficial effects as monotherapy than does SLM. However, this was detectable only by using the "indirect" stimulus adenosine 5'monophosphate, which is more specific in assessing changes in different components of airway wall inflammation than is MCh.

Adenosine Monophosphate↗
PubMed1997

Adult patients may outgrow their asthma: a 25-year follow-up study.

The present study investigated the outcome of asthma in a population of 181 adult patients 13 to 44 yr of age (median, 24 yr) who were extensively tested between 1962 and 1970 and in whom asthma was diagnosed. When retested 25 yr later, 38 subjects (21%) did not show bronchial hyperresponsiveness (BHR)(PC20 > 16 mg/ml), 45 subjects (25%) showed a FEV1 > 90% predicted, and 72 subjects (40%) did not report pulmonary symptoms. When absence of asthma was defined as no BHR, FEV1 > 90% predicted, and the absence of pulmonary symptoms reported by the patient, 20 subjects (11%) were no longer considered asthmatic when retested. Absence of asthma after 25 yr was associated with a younger age and less severe airway obstruction at first testing, odds ratios (OR) being 0.36 for age/10 yr, and 1.42 for FEV1/height2 (dl/m2). Absence of BHR was associated with a younger age, a higher FEV1, and a shorter untreated period (years between onset of asthma symptoms and specialized treatment of the disease) at first testing, and a lower total serum IgE level (IU/L) at second testing (OR, 0.48 for age/10 yr; OR, 1.37 for FEV1/height2; OR, 0.93 for untreated period; OR, 0.33 for log [IgE]). Neither sex nor atopy (one or more positive skin tests) were significant determinants of the outcome of both asthma and BHR. Our results suggest that in a substantial proportion of symptomatic asthmatics the disease improved, and that subsets may outgrow their asthma, even in adulthood. The data lend indirect support to the hypothesis that milder disease and earlier intervention are important for a beneficial outcome of asthma.

Adolescent↗
PubMed1997

Evidence for multiple genetic susceptibility loci for asthma.

Genetic susceptibility to asthma is due to multiple genes that interact with each other and the environment. There are many known environmental influences, such as viral and other respiratory infections and exposure to allergens, air pollutants, and active or passive cigarette smoke (1). Genome-wide screens for asthma and atopy have been completed and show statistical evidence for linkage in different racial groups and population samples (4, 5). Some of these linkages have already been replicated in different studies, and most of them are in chromosomal regions containing relevant candidate genes that may regulate inflammatory processes including cytokine synthesis, T-cell responses, or other immune functions. These associations support the relevance of this genetic approach in understanding susceptibility to and expression of asthmatic and allergic phenotypes. Once specific sequence variants are identified, it will become important to test for gene-environment interaction in order to understand the significance and relative effect of each gene on the overall phenotype.

Asthma↗
PubMed1997

Treatment of nocturnal airway obstruction improves daytime cognitive performance in asthmatics.

It has been shown that asthmatics have nocturnal symptoms associated with impaired cognitive performance. We explored more carefully different therapeutic approaches on this performance in relation to lung function in 46 atopics with mild to moderate asthma and with a circadian variation in peak expiratory flow (PEF) > or = 15%. In a double-blind, parallel study they inhaled salmeterol 50 microg or fluticasone 250 microg or a combination of both twice daily for 6 wk. The psychometric tests used informed about focused attention, mental flexibility, concentration, and attention. The results of the psychometric tests were compared with those in healthy control subjects. The PASAT score and the finishing time of the color-word chart subtest were significantly lower in these asthmatics than in the control subjects. Circadian PEF variation was the only independent factor significantly associated with impaired cognitive performance before the treatment period. The three treatment groups were equally effective in reducing circadian PEF variation below 10% and in improving FEV1 and bronchial hyperresponsiveness to methacholine (MCh) both day and night. After 6 wk of therapy, the daytime cognitive performance was improved to levels comparable to those of the healthy control subjects no matter which drug was inhaled. We conclude that a high level of circadian PEF variation (> or = 20%) has been associated with lower daytime cognitive performance in asthmatics. Reduction of circadian PEF variation to below 10% is an important goal of treatment in asthmatics.

Administration, Inhalation↗
PubMed1997

Mini-Wright peak flow meters are reliable after 5 years use. Dutch CNSLD Study Group.

In studies with a long-term follow-up, peak expiratory flow (PEF) meters are often used to assess bronchial obstruction. The question arises whether data obtained with these frequently used meters are still reliable after several years of use, and whether the old meters should be renewed after a certain period. In the present study, we tested the reliability of PEF values measured with mini-Wright PEF meters that had been used frequently for 5 yrs. The values obtained with these meters were compared with values measured with identical but new meters, in 50 patients with obstructive airways disease. Though statistically significant, there was no clinically significant difference in mean PEF measured with the old and new meters in most patients (mean difference 10.2 L.min-1). However, on an individual basis, the differences between old and new meters could be large (upper and lower limits of agreement (mean +/- 2 SD) being 63.6 and -43.2 L.min-1, respectively). We conclude that mean peak expiratory flow values measured with frequently used mini-Wright peak expiratory flow meters are still reliable after 5 yrs. In long-term studies, renewal of peak expiratory flow meters should be restricted to cases of obvious malfunction.

Equipment Failure↗